Effects of Viral Replication on Cellular Membrane Metabolism and Function

Abstract

As with the majority of cytolytic animal viruses, picornavirus infection leads to profound alterations in cellular membranes. Three types of changes are observed at late times of infection in cellular membranes: enhanced membrane permeability, proliferation of intracellular membranous vesicles, and inhibition of vesicular trafficking with the consequent blockage of protein glycosylation. This chapter focuses on both the structural and functional modifications that membranes of picornavirus (PV)-infected cells undergo during virus replication. Distinct portions of the vesicle membranes are very densely stained and thicker than typical intracellular membranes. PV 2B, 2BC, and 3A proteins are able to block glycoprotein transport when they are expressed individually in mammalian cells. Sedimentation of cytoplasmic extracts in sucrose gradients yielded viral RNA polymerase activity associated with the smooth membranes. Viral replication complexes from this fraction contain all types of PV RNA and several viral proteins involved in RNA replication. The sequence of protein 2B is one of the least conserved among picornaviruses. The permeabilizing activity of coxsackievirus B3 (CVB3) 2B has been implicated in virus release, since viruses carrying a mutant 2B protein exhibited a defect in virus yield. However, in the case of PV 2B, it has been reported that this protein is located mainly in the central portion of the cytoplasm, associated with the membranous vesicles that surround the viral replication complexes. PV protein 2C is a 329-amino-acid polypeptide that contains a typical nucleoside triphosphate (NTP)-binding domain. Its sequence is one of the most highly conserved among all picornaviruses.